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Novel Fusion Gene Transcripts and Targetable Mutations in High-Risk B-ALL With Exceptional Response to
Jifang Tu1,2, Huanping Wang1,2, Yungui Wang1,2
1Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Genes, Chromosomes & Cancer
|May 12, 2026
Summary
This study identifies four novel fusion genes in high-risk B-acute lymphoblastic leukemia (ALL). A patient achieved remission with venetoclax and modified COP therapy, suggesting a precision medicine approach for ALL.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer with diverse genetic drivers.
- Many ALL cases lack defined genetic subtypes, limiting targeted therapy options.
Purpose of the Study:
- To report a case of high-risk B-ALL with novel genetic alterations.
- To investigate the potential of deep genomic analysis for identifying therapeutic targets.
Main Methods:
- Whole exome sequencing and RNA sequencing were used to identify genetic abnormalities.
- The patient was treated with a modified COP regimen plus venetoclax.
Main Results:
- Four novel fusion genes (MAN1A1::GRIK2, ZCCHC7::CASC11, OSTM1-AS1::ZBTB24, IGL::BCL6) and mutations in CREBBP, BCL2, and ARID1B were identified.
- The patient achieved rapid and sustained complete remission.
Conclusions:
- Novel fusion genes, especially BCL6 rearrangements, may be key in B-ALL pathogenesis.
- Modified COP plus venetoclax shows promise for high-risk B-ALL with similar molecular profiles.
- Deep genomic analysis aids in discovering actionable therapeutic targets for precision medicine in ALL.
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